In the present study, we have elaborated the anti-inflammatory mechanism of MSM through homing of CD34+ stem cells towards an inflamed region by regulating hydrogen sulfide (H2 S) in an in vivo model of caerulein-induced acute pancreatitis (AP) and associated lung injury. Male Swiss mice were treated with hourly intraperitoneal injections of caerulein (50 μg/kg) for 6 h. MSM (500 mg/kg) was administered intraperitoneally 1 h after the first caerulein injection (therapeutic). The serum amylase activity and myeloperoxidase (MPO) activity in lung and pancreas were measured. The levels of H2 S and interleukin (IL)-1β, cystathionine-γ-lyase (CSE) and CD34+ expressions in pancreas and lungs were determined by RT-PCR and ELISA. Methylsulfonylmethane significantly ameliorated pancreas and lung histopathological changes, decreased serum amylase, MPO activity and inhibited caerulein-induced IL-1β expression. Furthermore, MSM reduced caerulein-induced H2 S levels by alleviating the expression of CSE in pancreas and lungs and increased CD34 expression and inhibited nuclear factor (NF)-κB translocation in caerulein-induced AP and associated lung injury. These findings indicate that MSM can effectively reduce inflammatory responses and induce the homing of CD34+ cells to the injured tissues.