〔Abstract〕 Objective To observe the effects of Xuefu Zhuyu decoction combined with thunder-fire moxibustion on limb pain, swelling and serum pain mediators after lower limb fracture. Methods A total of 75 patients with unilateral closed lower extremity fracture admitted to Zhengzhou Hospital of Traditional Chinese Medicine from January 2022 to December 2022 after surgical treatment were randomly divided into the observation group (38 cases) and the control group (37 cases). The control group was treated with cefuroxime sodium injection, and the observation group was treated with Xuefu Zhuyu decoction combined with thunder-fire moxibustion on the basis of control group. The pain score, swelling score and serum pain mediators [Substance P (SP), prostaglandin E2 (PGE2) and 5-hydroxytryptamine (5-HT)] levels before and after treatment were observed in the two groups before and after treatment, and the duration of swelling resolution, pain resolution and average length of hospital stay were compared between the two groups. Results Compared with the same group before treatment, visual analogue scale (VAS) scores of the two groups were decreased to varying degrees at 1 week and 2 weeks of treatment, and the VAS scores of the observation group were lower than those of the control group at 1 week and 2 weeks of treatment, the differences were statistically significant (P < 0.05). Compared with the same group before treatment, the swelling scores of the two groups were decreased to varying degrees after 1 week and 2 weeks of treatment, and the swelling scores of the observation group were lower than those of the control group after 1 week and 2 weeks of treatment, the differences were statistically significant (P < 0.05). The swelling regression time, pain regression time and average length of hospital stay in the observation group were significantly shorter than those in the control group, and the differences were statistically significant (P < 0.05). Compared with the same group before treatment, the serum levels of SP, PGE2 and 5-HT of the two groups were decreased to varying degrees after treatment, and the serum levels of SP, PGE2 and 5-HT of the observation group were lower than those of the control group after treatment, the differences were statistically significant (P < 0.05). No obvious adverse drug reactions occurred in the two groups, and the skin in the observation group did not appear red, swollen, pruritus, or ulceration. Conclusion Xuefu Zhuyu decoction combined with thunder-fire moxibustion can effectively relieve limb swelling after lower limb fracture, reduce the level of pain mediators, relieve pain degree, effectively shorten swelling, pain resolution time and average length of hospital stay.