Objective: To investigate the therapeutic effect of local arterial infusion (LAI) with low molecular weight heparin (LMWH) on severe acute pancreatitis in rabbits and its effect on the serum levels of TNF-α, IL-6 and IL-10. Methods: Twenty-four healthy adult rabbits were randomized into the sham operation group, SAP model group, SAP plus LMWH intravenous injection group (IV group) and SAP plus LMWH LAI group (LAI group). SAP model was established by injection with 5% sodium taurocholate under pancreatic capsule, and the rabbits of the two treatment groups were given LMWH (300 IU/kg) by intravenous injection or LAI, respectively. The serum levels of TNF-α, IL-6 and IL-10 in rabbits of each group were detected at 0.5, 3, 6 and 12 h after surgery and the pathological changes of pancreatic tissues were also assessed. Results: After surgery, the serum levels of TNF-α and IL-6 of the sham operation group were slowly elevated, while those of the remaining groups were markedly increased within 0.5 to 6 h, that all had statistical differences compared with the sham operation group (P<0.05 or P<0.01), and then gradually declined. The serum levels of TNF-α and IL-6 of the IV group and LAI group were all significantly lower than those of the SAP group at each observation time point (P<0.05 or P<0.01) and, further, the decreasing degrees of the two factors in the LAI group were more pronounced than those in the IV group (P<0.05 or P<0.01). The level of IL-10 of the sham operation group had no obvious alteration over the observation period after surgery, while it was markedly decreased in the SAP group at each time point after 6 h and all had statistical differences compared with the sham operation group (all P<0.01). The level of IL-10 of the IV and LAI group markedly increased with statistical differences compared with the SAP group (P<0.05 or P<0.01) and, furthermore, its increasing degree in the LAI group was more pronounced than that in the IV group (P<0.01). Except for the sham operation group, all the pancreatic tissues of the other groups exhibited pathological characteristics of SAP with varying degrees, among which the most severe was in the SAP group, less in the IV group, and least in the LAI group. Conclusion: LMWH can decrease the TNF-α and IL-6 levels, and increase the IL-10 level in rabbits with SAP. LMWH has therapeutic effect on SAP and its local arterial injection is more effective than intravenous injection.