Both fish and flaxseed oils are major sources of different n-3 fatty acids. Beneficial effects of fish oil on post-transplantation complications have been reported. The current study aimed to compare the effects of flaxseed and fish oils in a rat cardiac allograft model. Male Fischer and Lewis rats were used as donors and recipients, respectively, to generate a heterotopic cardiac allograft model. Animals were randomly assigned into 3 groups and fed a diet supplemented with: a) 5% w/w safflower oil (control n=7), b) 5% w/w flaxseed oil (n=8) or c) 2% w/w fish oil (n=7) and an i.p. injection of cyclosporine A (CsA) (1.5 mg/kg/d) over 12 weeks. Body weight, blood pressure, plasma levels of lipids, CsA, select cytokines as well as graft function and chronic rejection features were assessed. Body weight and blood CsA levels were similar among the groups. Relative to controls, both treated groups had lower systolic and diastolic blood pressure and plasma levels of macrophage chemotactic protein-1 (MCP-1). Treatment with fish oil significantly (P<0.05) lowered plasma levels of TG, TC, and LDL-C. HDL-cholesterol concentrations were significantly higher (P<0.05) in the flaxseed oil-treated group as compared to the other two groups. Both Flaxseed oil and fish oil may provide similar biochemical, hemodynamic and inflammatory benefits after heart transplantation, however, neither of the oils was able to statistically significantly impact chronic rejection or histological evidence of apparent cyclosporine-induced nephrotoxicity in this model.