Martin Arrowsmith and his wife Leora bounce around to a couple of places in this book, including New York, Chicago, the Midwest, and even the Caribbean. But Sinclair Lewis' most vivid descriptions of setting always come out when the couple goes to small-town America, the setting in which Sinclair Lewis grew up. When they move to the small town of Wheatsylvania, for example, we learn that Martin
… could have walked around the borders of Wheatsylvania in ten minutes. Probably to Leora one building differed from another […] but to Martin the two-story wooden shacks creeping aimlessly along the wide Main Street were featureless and inappreciable. (9.3.9)
When it comes to his setting, Lewis never misses a chance to make a satirical poke at small town life. That's the kind of humor that made him a bestseller in the first place, and if you read closely, you'll really notice how much more description he gives to small towns compared to big cities… because he has so much fun ridiculing them.
Oh, and fun fact: Lewis' razor-sharp satire prompted him to create the fictional state of Winnemac, where Martin Arrowsmith attends med school.
People were super-peeved when Lewis poked fun at small town Minnesota in Main Street, so he decided to set his novels in Winnemac (which is equal parts Wisconsin, Minnesota and Michigan). Five of his novels take place in Winnemac: Babbit, Arrowsmith, Elmer Gantry, Dodsworth, and Gideon Planish.