"I got pulled over probably 30-plus times because people would call in saying there was some guy pushing a little kid in a stroller out on the highway," he said. Soon, he knew just to stand patiently and hand them his driver's license. "I got it down to a science."
Other people he met, he said, were beyond friendly. Once he began running through the southern states, people would stop to hand him water, money and food.
"I don't know if they thought I was homeless, but it was pretty nice," he said.
In Arkansas, one woman "just pulled up in an SUV and handed me a bag and said 'this is lunch' and drove off. When he looked inside he found $10, her business card and a chicken sandwich.
He later called the woman to explain what he was doing and she was so enthusiastic she contacted her friends in Mobile, Ala., via Facebook and arranged for them to feed him when he ran through. She also reached out to friends in Florida to help Knowlton's mother arrange for his finish line victory.
And just as he was about ready to finish off his fifth pair of running shoes, a couple that pulled up beside him to find out what he was up to, went out and bought him a sixth pair to reach the finish.
But the kindness of strangers was not always enough to overcome the difficulties of the trip.
"There was always something that came up," he said, ticking off wind and rain and roads with no shoulders as common foes on the road.
He suffered through shin splints, weight loss and swollen ankles, vowing not to take the advice of others and rest even one day.
"I thought if I take one day off it might get easier to take days off," he said.
Dr. Linn Goldberg, head of the Oregon Health and Science University's Division of Health Promotion and Sports Medicine, said people who engage in such continued extreme exercise run the risk of not only injury, but reduced levels of testosterone in men, breakdown of muscles and inadequate hydration.
"This is not healthy, although that is not a problem in the U.S. with most people being overweight or obese and few getting enough exercise to impact their health," he wrote of Knowlton's run in an e-mail to ABC News. "It is not only an amazing feat, he must have amazing feet!"
It was a feat that seemed laughably unimaginable 25 years ago.
Ever since he was diagnosed with the disease as a teenager, Knowlton has endured years of illness, and countless what-ifs.
At 18, he underwent surgery to remove ulcers.
"I've never had to have surgery again, but within a couple of years after the surgery it came back," he said. In his 20s, after years of flare-up and constant worry, Knowlton said he took control.
"I said. 'I'm done ... having to worry about what I eat and every little thing I do. I just want to live like a normal person,'" he said.
Despite the need for a few rounds of steroids every so often to treat flare-ups, Knowlton said he's doing well.
He was cognizant, however, of the lack of privacy at many points in his route should he need to make a pit stop.
"I had a few problems during the run," he said. ""There was a lot of places where there was no trees or places to hide."
Knowlton, who kept a website and a blog updated during his run, said he has raised between $4,000 and $5,000 for the Crohn's and Colitis Foundation of America, (CCFA), and hopes the post-run attention he's been getting will lead to more.