Immune infertility has gained impetus in recent years. Various scientific studies have been carried out on the toxic effects of lead on immune function; however, uncertainties still persist. The present study addresses the immunomodulatory effects of testicular macrophages caused due to lead exposure (in-vivo). In mice, lead has a primary effect on the testes, and acts at all levels of the reproductive as well as the testicular immune response. The study was undertaken to investigate the effects of lead acetate on immune system in Swiss albino mice and the underlying mechanism of pro-inflammatory cytokine action. The immunomodulatory effects of lead are complex and appear to involve multiple pathways, not all of which are fully understood. Testicular macrophage dysfunctions by lead was studied by calculating morphological alteration and associated cell functions of innate immunity followed by estimation of pro-inflammatory cytokine release (TNF-α). The present work shows that lead is responsible for a significant morphological alteration, reducing cell function in testicular macrophages probably by increasing oxidative damage whereas increase in TNF-α release was also observed which increased inflammation. Results demonstrated that lead intoxication leads to increase in pro-inflammatory response. TNF-α is probably unable to bind with the surface receptor in testicular macrophages because of altered morphology which reduces cell function and ultimately causes reproductive dysfunction.