Intermittent fasting (IF) is a dietary approach against obesity; however, investigations on its role in male fertility showed contradictory results. Aims. As nuclear factor erythroid 2-related factor 2 (NRF2)/mitogen-activated protein kinase p38 (MAPK)/nucleotide-binding oligomerization domainlike receptor with a pyrin domain 3 (NLRP3) signaling pathways regulate inflammation and pyrotosis, this study aimed to elucidate whether these pathways are involved in the underlying molecular mechanisms and to investigate the prophylactic effects of IF on male reproduction dysfunction in obese rats. Methods. Twenty-four adult rats were divided as follows: Control lean (CL), control positive (CP), which were fed standard diet for four non-consecutive days/week, with alternate fasting on the other 3 days (24 h fasting), high-fat diet group (HFD), and the HFD-fasting group (HFD-IF), which was fed a HFD, followed by fasting protocol as in CP group. Serum testosterone, inflammatory markers, semen analysis, testicular malondialdehyde (MDA) concentration, and superoxide dismutase (SOD) activity were measured. Also, testicular and epididymal histological study, immunohistochemical analysis of NLRP3 and NRF2 and reverse-transcription quantitative polymerase chain reaction (RT-qPCR) for mRNA expression of SIRT1, NRF2, p38AMPK and NLRP3 were performed. Key results. Combining IF with HFD limited rats’ testicular spermatic and steroidogenesis impairment, histopathological alterations, by upregulating SIRT1/NRF2 and downregulating p38 MAPK/NLRP3 signaling pathways versus the HFD group. In the HFD-IF group, oxidative and inflammatory markers had a significant decrease versus in the HFD group. Conclusions. IF has a beneficial effect on male reproductive health and emphasizes the significance of customized dietary strategies for addressing male fertility issues. Implications. Further investigation is required to clarify more prophylactic mechanisms of IF.