Background Epidermal burn injury may trigger significant apoptosis of the spleen cells, which might be caused by a burn-induced systemic inflammatory reaction. Heparin has been shown to possess anti-inflammatory properties. Interleukin 1 (IL-1) is centrally important among pro-inflammatory cytokines. We hypothesized that heparin might inhibit burn-induced apoptosis in the spleen via suppression of the IL-1 pathway. Methods Burn injury was performed on IL-1 R+/+ ( IL-1 receptor wild-type mouse) and IL-1 R-/- (IL-1 receptor knockout mouse) mice, and they were then treated with heparin, saline or IL-1 receptor antagonist IL-Ra. Apoptosis, IL-1á and IL-1β expression were assessed in the spleens and serum. Survival curve analysis was further applied to elucidate the mechanism of heparin’s protective properties. Results Burn induced significant apoptosis (sham: 3.6%±2.1% vs. burn: 28.8%±5.9%; P <0.001) and remarkable expression o IL-1á and IL-1β in the mouse spleens and serum. Heparin reduced the burn-induced apoptosis in the spleens (heparin treated: 8.6%±3.4%, P <0.005), which could be blocked by IL-1Ra. Heparin markedly decreased both IL-1α and IL-1β expression in the spleens and serum of burned mice. IL-1 R-/- mice demonstrated considerably less apoptosis in the spleens and had a higher survival rate after burns. Heparin did not significantly decrease apoptosis in the spleen and the mortality rate in IL-1 R-/- mice after burns. Conclusion Heparin inhibits burn-induced apoptosis of the spleen cells by suppressing IL-1 expression in mice.