Objective To study the efficacy and safety of celecoxib combined with methotrexate in the treatment of rheumatoid arthritis. Methods A total of 100 patients with rheumatoid arthritis who were treated in our hospital from April 2014 to May 2016 were selected as subjects. All patients were divided into study group and control group according to the random number table method, each group of 50 cases. The control group was treated with methotrexate. The study group was treated with celecoxib on the basis of the control group. The levels of arthritis, inflammatory factors (IL-1, IL-6), the number of joint swelling and the incidence of adverse reactions were observed and compared between the two groups before and after treatment. Results The VAS scores of the two groups were lower than those before the treatment, and the difference was statistically significant. The levels of IL-1 and IL-6 in the two groups were lower than those before treatment, and the difference was statistically significant. The number of joint swelling after treatment in the two groups was less than that before treatment, and the study group was less than the control group, the difference was statistically significant; There was no significant difference in the incidence of adverse reactions between the two groups ［8.0% vs12.0%］. Conclusion Celecoxib combined with methotrexate in the treatment of rheumatoid arthritis with significant efficacy, high safety, can effectively reduce the inflammatory response, reduce joint pain in patients with joint swelling, reduce the number of joint swelling, improve patient quality of life, worthy of clinical promotion.