We aimed to investigate and compare the effects of rapid (NaHS) and slow (GYY4137 and AP39) hydrogen sulfide (H2 S) releasing donors on LPS-induced tracheal hyperreactivity and pro-inflammatory cytokine levels in lung tissues of mice. Tissues were isolated from male BALB/c mice and incubated with LPS (10µg/mL) in tissue culture. The subgroups were incubated with NaHS, GYY4137 and mitochondria-targeted donor AP39. LPS incubation did not alter contraction response to carbachol, but enhanced 5-HT and bradykinin-induced contractions in tracheal rings, and elevated IL-1β, IL-6 and TNF-α levels in lung homogenates. NaHS at 300µmol/L and 1000µmol/L, GYY4137 at 30µmol/L and 100µmol/L, and AP39 at 30nmol/L concentrations inhibited the tracheal hyperreactivity to 5-HT, whereas none of these donors affected the enhanced contraction to bradykinin. GYY4137 was also effective to inhibit 5-HT hyperreactivity acutely. In lung tissues, NaHS prevented the elevation of IL-1β level at 1000μmol/L, and IL-6 and TNF-α levels at 100μmol/L concentrations. Incubation with GYY4137 (100µmol/L) and AP39 (30nmol/L and 300nmol/L) inhibited the increase in IL-6 and TNF-α levels, but not IL-1β at concentrations that they affected tracheal hyperreactivity. These results indicate that H2 S donors can decrease inflammation and prevent airway hyperreactivity.