Experimental studies have suggested an important role of the spleen in lipid metabolism, although with controversial results. Our purpose was to analyze the effect of a nutritionally balanced (NB) diet and a diet containing pork fat (PF) as source of lipids on the lipid profile of rats submitted to splenic surgery. Sixty adult male Wistar rats were divided into six groups of 10 animals each: 1 sham-operated, NB diet; 2 sham-operated, PF diet; 3 total splenectomy (TS), NB diet; 4 TS, PF diet; 5 TS followed by splenic autotransplantation (SA), NB diet; and 6 SA, PF diet. Blood samples were collected at the beginning (D0) and after 12 weeks of the experiment (D + 12) for plasma lipid determination. Morphologic regeneration of splenic tissues was observed, with no differences between groups 5 and 6. When D + 12 plasma lipid levels were compared to D0 levels there were no differences in groups 1, 3, and 5, while in groups 2, 4, and 6 total cholesterol (TC), low density lipoprotein (LDL), very low density lipoprotein (VLDL), and triacylglycerols (TAG) increased, and high density lipoprotein (HDL) decreased. At D + 12, groups 2, 4, and 6 had lower HDL than group 3. In conclusion, regardless of the surgical procedure applied to the spleen, an NB diet maintained plasma lipid levels while a diet with PF as source of lipids changed the animals' lipid profile.