Objective To explore clinical efficacy of elephantiasis myogenic cream for treatment of chronic refractory skin ulcer. Methods A total of 91 chronic refractory skin ulcer patients were randomized into the treatment group (n=46) and the control group (n=45) by random number table method. Patients of control group were treated with conventional debridement, while the treatment group were treated with elephantiasis myogenic cream. The two groups were treated for 4 weeks. Clinical curative effect was evaluated after treatment. The pain score at the times of debridement and ulcer wound healing time of the two groups were compared. The FGF-2, VEGF and fiber connection (Fn) of wound secretion of the two groups before and after treatment were compared. Results Total effective rate of treatment group was 87.0％ (40/46), which was significantly higher than the control group 66.7％ (30/45), and the difference was statistically significant (χ2=5.275, P=0.022). The pain score at the time of 2 w and 4 w after treatment in the treatment group were significantly lower than those in the control group (t value were 10.456, 12.266, all Ps<0.01). After treatment, ulcer wound healing time in the treatment group were significantly lower than those in the control group (t=2.911, P=0.002). After treatment, the FGF-2 (7.72 ± 0.58 ng/ml vs. 6.37 ± 0.50 ng/ml, t=11.881), VEGF (24.85 ± 5.63 ng/ml vs. 18.75 ± 4.51 ng/ml, t=5.697) and Fn (4.15 ± 0.42 ng/ml vs. 3.47 ± 0.38 ng/ml, t=8.093) of wound secretion in the treatment group were significantly higher than those in the control group (P<0.05).There were no serious adverse reaction of the two groups during treatment. Conclusions The elephantiasis myogenic cream for treatment of chronic refractory skin ulcer has a good efficacy and low adverse reactions, can relieve patients' pain, improve the wound heal, reduce heal times.