Introduction: Spleen is the largest secondary lymphatic organ in the body designed to respond immunologically to antigens circulating in blood. Spleen performs important functions such as red blood cells production, their destruction, blood filtration, storage of blood and phagocytosis. Most of the textbooks of microscopic anatomy show picture of human spleen as the combination of findings derived from various animals. Aim: The present study was undertaken to compare histological difference between human and dog spleen as they differ according to their functions. Material and methods: Five mature dog and five normal human spleens were procured and were kept in Bouin’s fluid for fixation. Sections were cut after paraffin embedding. Slides were stained by Haematoxylene and Eosin, Masson’s Trichrome, Gordon and Sweet’s reticular stain and observed under light microscope. Results: Capsule and trabeculae contains collagen and elastic fibers with few smooth muscle fibers in human spleen while in dog spleen more smooth muscle fibers and few elastic fibers were present. White pulp was more in human than dog. Red pulp and marginal zone of dog spleen showed ellipsoids and penicillar arteries which were poorly defined in human spleen. Red pulp showed prominent venous sinuses in dog spleen than human. Conclusion: Histological features are well defined in storage type of spleen as in dog than the defensive human spleen. Histological features of dog spleen are useful in better understanding of microscopic anatomy and can be used for teaching purpose.