The present study analyzes the efficacy of N-acetyl cysteine (NAC) against diazinon (DZN)-induced nephrotoxicity in male Wistar rats. Rats were divided into five groups with six animals in each group: Group 1 (G1) was maintained in typical control circumstances and given saline once daily intragastric (IG) for 4 weeks; G2 was administered 0.1 mL olive oil IG for 4 weeks; G3 was administered IG NAC 150 mg/kg daily as an aqueous solution for 4 weeks; G4 was administered IG diazinon at a dose of 15 mg/kg daily for 4 weeks; and G5 was administered IG NAC daily one hour before diazinon at the same dose in G3 and G4 for 4 weeks. Sub-chronic exposure to DZN impairs the kidney structure and function, as evidenced by the histopathology, immunohistochemistry, and gene expression of NLRP3, NFκB, IKB, BCL2, BAX mRNA. Our findings showed that NAC reduces the renal dysfunctions induced by DZN by restoring urea and creatinine levels as well as oxidative indicators. Moreover, serum inflammatory markers (IL-1β and TNF-α) concentrations were ameliorated by NAC treatment. However, NAC has shown to play a beneficial role against nephrotoxicity by reversing the cytoarchitecture and downregulation of inflammatory (NLRP3, NFκB, IKB) and apoptotic (BAX) as well as upregulated BCL2 genes and proteins in kidney tissues, bringing them to near-normal levels. Moreover, IHC examination of renal tissue revealed the attenuation of expression of TNF-α. Therefore, NAC could be potentially used to protect the kidneys from pathological changes induced by DZN.