The Legume Inflammation Feeding Experiment is, to our knowledge, the first randomized crossover feeding trial testing the effects of a legume-enriched, low-glycemic index (GI) diet among men characterized for colorectal adenomas and insulin resistance (IR) status. This study was designed to test the effects of a legume-enriched diet compared with a healthy American (HA) diet under weight-stable conditions. The primary objective was to assess effects on C-reactive protein (CRP) and C-peptide levels. The secondary objective was to assess changes by IR status or history of adenomas. A total of 64 men who completed a colonoscopy within the previous 2 y consumed 2 diets in random order each for 4 wk separated by a washout period. The diets were a legume-enriched (250 g/d), low-GI (GI 38) diet and a high-GI (GI 69) HA diet. We measured fasting glucose, insulin, C-peptide, CRP, and soluble tumor necrosis factor-alpha receptors I and II (sTNFRI/II) at the beginning and end of the diet periods. Participants who consumed both the legume and HA diets had favorably improved CRP (-20.2 and -18.3%) and sTNFRI (-3.7 and -4.4%) concentrations, respectively. The sTNFRII concentrations declined marginally during the legume diet period (-3.8%; P = 0.060) and significantly during the HA diet period (-5.1%; P < 0.001). Fasting glucose increased significantly during both the legume (+1.8%) and HA (-2.2%) diet periods. Only the changes in glucose differed between the diet periods. Serum C-peptide and plasma insulin levels did not change in participants consuming either diet. Healthful dietary changes can improve biomarkers of IR and inflammation.