Objective To investigate the effect of intraperitoneal administration of pentoxifylline on the development of hyperalgesia and the activation of glial cells in a rat model of postoperative pain. Methods Sixty male SD rats weight 190 g-220 g were randomly divided into 2 groups: control group (NS group) and treatment group (PTX group), in which 50 mg/kg saline vehicle or pentoxifylline (n=30) was given intraperitoneally 15 min before surgery and continued once a day to the 5th day after the operation, respectively.The animal model of postoperative pain was established by incision hind paw. Cumulative pain score and paw withdrawal threshold were measured at 1 d before operation and then at 1, 2, 3, and 5 h and 1, 2, 3, and 5 d after operation.Spinal cord tissue samples from rats were taken for analysis of glial fibrillary acid protein (GFAP) and ionized calcium bindingadaptor molecule-1 (Iba-1) expression by means of immunohistochemistry at the following times after operation: 1, 2, 3, and 0.8, 6.6±0.5, 8.6±0.7, 10.2±0.4, 7.0±0.6 and 5.6±0.5 in the PTX group respectively, less than the NS group with 4.0±0.6, 6.0±and 3 d, the PWT were (5.8±1.6), (5.2±1.1), (4.4±0.6), (4.9±0.4), (5.2±1.1), (7.6±1.8) and (10.4±1.6) g in the PTX group respectively, more than the NS group with (2.4 ±0.8), (2.1±0.5), (2.0±0.5), (2.1±0.3), (2.3±0.5), (4.5±0.9)and(8.1±1.4) g 205.6±4.2 and 230.2±3.2 in the PTX group respectively, lower than the NS group with 244.1±4.9, 258.6±4.12 and 276.2±3.4 (P＜the PTX group respectively, lower than the NS group with 230±3 and 205±4 (P＜0.05). Conclusion Pentoxifylline can attenuate the process of mechanical allodynia in a rat model of postoperative pain, its main mechanism may be related to the inhibition of glial cells activation in the spinal cord.