Background Postsurgical peritoneal adhesions (PPAs) are pathologic fibrous bands within the peritoneal cavity. The aim of this study was to investigate the protective effect of hydrogen-rich saline (HRS) on PPAs formation in mice. Material/Methods Adhesions were induced in mice using the cecum rubbing model. The mice were allocated into 4 groups: control sham group without cecum rubbing; PPA group with saline applied intraperitoneally (i.p.) daily after cecum rubbing; PPA+HRS (5) group with 5 ml/kg of HRS applied i.p. daily after cecum rubbing; and PPA+HRS (10) group with 10 ml/kg of HRS applied i.p. daily after cecum rubbing. On the 1st, 3rd, and 7th days after the operation, mice were killed and pathological adhesion bands were quantified to detect the effect of HRS on PPAs formation. Results HRS did not affect PPAs formation on the 1st day, but did make a significant reduction on the 3rd and 7th days. A significant increase of t-PA and decrease of TGF-β1 and PAI-1 in the peritoneal fluids were observed in the HRS-treated groups. The levels of MDA and MPO in the HRS-treated groups were significantly lower than those in the PPA group. TNF-α and IL-6 levels in HRS-treated groups significantly decreased compared with those in the PPA group on postoperative day 3 and 7. Moreover, HRS decreased the mRNA levels of pro-inflammatory cytokines and TGF-β1 expression in the postsurgical adhesion bands. Conclusions These results showed that HRS had therapeutic potential for preventing PPAs formation, possibly through balancing the expression of TGF-β1, t-PA, and PAI-1, and inhibiting oxidative stress and inflammation.