Early studies have documented that PM_2.5 can not only induce cardiac tissue toxicity, but can adversely affect the performance of the myocardium and deteriorate its tolerance to withstand ischemia-reperfusion (IR) injury. The primary factor that contributes to the adverse impacts of PM2.5 exposure on the heart is subcellular changes, with particular emphasis on mitochondrial dysfunction, inflammation, oxidative stress, and deterioration of pro-survival signaling pathways. Despite the ongoing efforts to uncover the mechanistic changes induced in the heart by PM2.5 exposure, no studies have presented strategies for mitigating PM2.5-induced cardiotoxicity or enhancing the tolerance of the myocardium to withstand IR injury. Considering the potential of hydrogen sulfide, a gasotransmitter known to protect the heart from pathologies linked to oxidative stress and mitochondrial dysfunction, we explored the efficacy of H2S in attenuating PM2.5-associated increased IR injury. Female Wistar rats were exposed to 250ug/m³ of PM2.5 for 3 hours daily for 21 days, after which the hearts were isolated and mounted on an isolated rat heart apparatus. H2S was administered directly to the PM2.5-exposed hearts, after which the hearts were subjected to 30 min of ischemia and 60 min of reperfusion to induce IR injury. Our results revealed that the ability of the PM2.5-exposed myocardium to withstand IR injury had considerably improved. The pivotal mechanism driving these beneficial changes was the preservation of mitochondrial function (improved bioenergetics, respiration) along with quality control mechanisms. The improvement in mitochondrial function was also reflected in terms of reduced oxidative stress and activation of pro-survival signaling pathways. Based on these findings, we concluded that hydrogen sulfide holds promise as a potential therapeutic agent for enhancing the myocardium's resilience to additional stressors in the form of IR injury.