Background <p>Varicocele (VC) is a common cause of male infertility, and traditional Chinese medicine has shown therapeutic promise in treating VC-associated infertility.</p> Objective <p>This study aims to investigate the protective effects of Tongyu Qiangjing Decoction (TQD) on spermatogenesis in an experimental rat model of VC and to explore the underlying mechanisms.</p> Methods <p>A rat model of VC was established using the renal vein ligation technique. Rats were treated with either inhibitors of the NOD-like receptor protein 3 (NLRP3)/Caspase-1/Gasdermin D (GSDMD) pathway or varying doses of TQD. After treatment, left testicular and epididymal tissues were collected, and organ indices were calculated. Sperm parameters, including concentration, motility, viability, and morphology, were measured. Hematoxylin and eosin staining was performed to observe testicular histopathological changes. Immunofluorescence staining was used to detect SOX9. Western blot was carried out to quantify NLRP3, Caspase-1, and GSDMD. Reactive oxygen species in the testes were measured using fluorescence probes and flow cytometry. The inflammatory cytokines were quantified by enzyme-linked immunosorbent assay, and oxidative stress markers were assessed biochemically. Sertoli cells (SCs) were isolated from rat testes and cultured under hypoxic conditions to mimic the effects of VC. Cells were treated with various concentrations of TQD-containing serum, and cell viability, toxicity, and pyroptosis markers were evaluated.</p> Results <p>Induction of VC resulted in significant testicular damage, impaired spermatogenesis, and a decrease in Sertoli cell numbers, along with activation of the NLRP3/Caspase-1/GSDMD pathway. Blockade of this pathway reversed the testicular damage, restored spermatogenesis, and preserved Sertoli cell integrity in the VC rat model. Treatment with TQD also improved testicular function, spermatogenesis, and SC number in a dose-dependent manner, and inhibited NLRP3/Caspase-1/GSDMD pathway activation. TQD-containing serum treatment prevented pyroptosis in SCs, also in a concentration-dependent manner.</p> Conclusion <p>TQD improves spermatogenesis in VC rats by blocking the NLRP3/Caspase-1/GSDMD pathway and preventing SC pyroptosis.</p>