Objective To investigate the effect of Huoxue Zhitong decoction combined with manual reduction and small splint fixation on the improvement of clinical symptoms, wrist range of motion and serum level of pain mediators in patients with distal radius fracture. Methods A total of 44 patients with distal radius fractures admitted to Affiliated Hospital of Jiangnan University from January 2018 to December 2020 were selected and divided into the control group (22 cases) and the observation group (22 cases) according to random number table method. Patients in the control group were treated with manual reduction and small splint fixation, and underwent routine grasping rehabilitation training after treatment, patients in the observation group were treated with Huoxue Zhitong decoction on the basis of the above treatment methods, patients in both groups were treated for 4 weeks and followed up for 4 weeks after treatment. The clinical effect, improvement time of clinical symptoms, wrist range of motion and serum level of pain mediators before and after treatment, as well as the complicationsoccurred during following-up were compared between the two groups. Results The total clinical excellent and good rate in the observation group was higher than that in the control group; the time of fracture healing, the time of pain disappearance and the time of swelling disappearance of patients in the observation group were shorter than those in the control group; compared with before treatment, the degrees of pronation, supination, back extension, palm flexion and radial deviation of patients in the two groups increased after treatment, and the observation group was higher than the control group; the serum levels of substance P (SP), β-endorphin (β-EP), prostaglandin E2 (PGE2) and neuropeptide Y (NPY) of patients in the two groups decreased after treatment, and the observation group was lower than in the control group; during the following-up period, the total incidence of complications of patients in the observation group was lower than that in the control group (all P<0.05). Conclusion Huoxue Zhitong decoction combined with manual reduction and small splint fixation for the treatment of distal radius fracture, which can promote the improvement of clinical symptoms, improve wrist range of motion, reduce the body's pain response, and has a high safety.