Hydrogen sulphide (H2S) is a gas transmitter that plays a vital role in a variety of physiological and pathological processes. Xenoestrogen (XE) a regularly used manufacturing chemical, has been related to endocrine disruptor. The purpose of this study was to investigate the effects of H2S donor (sodium hydrogen sulfide [NaHS]) on xenoestrogen (XE)-induced toxicity in rats. Twenty four adult female rats were divided into three groups: group I: control group, group II rats were intraperitoneally (IP) injected with XE (150 mg/kg body weight/ day) dissolved in corn oil for 4 weeks, group III rats were IP injected with H2S donor NaHS intraperitoneally (IP) at daily dose of 5 mg/kg body weight/day dissolved in deionized water for 6 weeks and were injected with XE as group II. Biomarkers including lactate dehydrogenase (LDH), Interleukin 6 (IL- 6), inducible nitric oxide synthase (iNOS), hypoxia-inducible factor 1 alpha (HIF 1α), caspase-3 were determined and lymphocytes %.The obtained results revealed that ingroup 3, a significant decrease in serum LDH, lymphocytes %, iNOS, with marked decrease in serum Caspase-3when compared to group II. These results suggest that H2S might ameliorate XE induced-toxicity via its anti-inflammatory and anti-apoptotic effects.