Dietary red and processed meats may increase risk of colorectal cancer (CRC), whereas fiber may be protective. Recently, we demonstrated that dietary beef causes greater colonic DNA strand breakage than equivalent levels of chicken in rats and that resistant starch (RS) as 20% high amylose maize starch (HAMS) attenuated the damage. From that study, we now report measures of circulating factors that may influence CRC initiation or progression including malondialdehyde (MDA), leptin, insulin-like growth factor-I (IGF-I), insulin, matrix metalloproteinase-2 (MMP-2), tissue inhibitor of MMP-2 (TIMP-2), interleukins (IL), and short chain fatty acids. MDA levels were increased by beef diets relative to the chicken diets. Leptin concentrations, which were lower for chicken than beef at the 35% level in the absence of HAMS, were lowered by HAMS. Higher dietary chicken (but not beef) increased IGF-I irrespective of HAMS feeding. Higher levels of chicken resulted in greater insulin concentrations than for beef in rats fed HAMS. Without dietary HAMS, TIMP-2 concentration increased in response to both meats but was highest for chicken. MMP-2 and TIMP-2 concentrations were higher for HAMS diets. IL-1beta and IL-12 concentrations were lowered by HAMS feeding. Colonic DNA strand breakage was positively associated with circulating leptin and MDA concentrations as well as tissue MDA concentrations and negatively associated with plasma TIMP-2 concentration. MMP-2 and TIMP-2 positively correlated with hepatic portal butyrate levels but leptin concentrations correlated negatively. These results suggest diets high in meat or RS could influence cancer initiation or progression by changes in circulating levels of hormones and other factors.