I use the 20.2.125 puncture resistant tubes with Tomos 2.25 tires, and they are a perfect fit. A 2.50 tire might be stretching it a bit, you would almost certainly have to overinflate it, and that would place more stress on the tube. I would have to say I don't recommend it, but you can try it, as long as you realize you have something that is potentially unsafe, and ride it accordingly, and see what happens. Peace. Jerry.