The aim of the study was to compare the effects of silver salt and silver nanoparticles on the epididymis morphofunctional state of obese rats. Animals in the control group received a standard diet. Rats in which obesity was modeled were divided into several groups that received a silver salt solution and a silver nanoparticle solution for 10 days, respectively. After the end of the experiment, the epididymis was removed from the animals. In the epididymis, epithelial cells were studied in three zones: the head, body, and tail. It has been shown that in obesity, secretory activity increases in the head and body of the organ along with inhibition of synthetic function, and in the tail zone the functional state of cells decreases. The administration of silver nitrate to obese rats differently affects the synthetic and secretory activity of epithelial cells in different areas of the epididymis, depending on the dose. Administration of 0.5 ml/100 g has a more powerful effect on the morphometric parameters of epididymal cells than 0.25 ml/100 g. Silver nanoparticles also dose-dependently affect the morphofunctional state of epididymal cells in obese rats. At a dose of 0.25 ml/100 g, silver nanoparticles cause activation of cells in different parts of the organ, but at a dose of 0.5 ml/100 g, there is mainly a decrease in the secretory activity of epithelial cells, especially in the head of the epididymis. In general, different areas of the epididymis respond ambiguously to the administration of silver preparations. Nanoparticles have a more powerful effect on the studied parameters than silver nitrate. Additional studies are needed to establish the dose-dependent effect of silver preparations on the functional state of the epididymis.