The use of fish oil (FO) as a dietary supplement to prevent or reduce the severity of cardiovascular diseases and autoimmune disorders such as rheumatoid arthritis is receiving much attention. Several recent reports indicate that eating fish often or the use of small doses of FO capsules appears to have benefits against cardiovascular diseases. We have reported in the past that diets enriched with FO protect against renal diseases and prolong the life span of autoimmune-prone mice compared to corn oil (CO) diets. However, the optimum ratio of eicosapentaenoic acid (EPA) to docosahexaenoic acid (DHA) in commercially available FOs to reduce the production of various pro-inflammatory cytokines has not been well established. We, therefore, obtained deodorized FO from three sources containing different EPA/DHA contents, fed them to C57BL/6 mice for 8 weeks in a 10% (vol/wt) diet (oil A, 11/10; oil B, 14/9; oil C, 23/14) and compared them with (10%) CO-fed mice as control. TNF-alpha, IL-6 and IL-1beta were measured by enzyme-linked immunosorbent assay in thioglycollate-induced macrophages, 8 and 24 h after lipopolysaccharide treatment. The results showed a significant decrease in TNF-alpha after only 8 h in oil C. After 24 h, TNF-alpha, IL-6 and IL-1beta levels decreased only in mice fed oil C, although nonsignificant decreases were seen in mice fed oil A compared to mice fed CO. The antioxidant enzymes, catalase and glutathione transferase, were higher in kidneys of mice fed oil C compared to mice fed CO. The study suggests that anti-inflammatory activity may vary among different sources of FO due to variations in EPA/DHA content.