The purpose of this study was to examine whether glucosamine has an antirheumatic effect in a randomized placebo-controlled study. The subjects were 51 rheumatoid arthritis (RA) patients: 25 patients in the glucosamine group and 26 patients in the placebo group. Glucosamine hydrochloride at a daily dose of 1,500 mg and placebo, respectively, were administered for 12 weeks along with conventional medication. While significant improvement was not found in joint counts and in the rate of ACR20 responders, the face scale and a visual analogue scale pain were significantly in favor of the glucosamine group. ESR and CRP levels did not change, but serum MMP-3 levels decreased in the glucosamine group. Results of the patients' self-evaluations and the physicians' global evaluations indicated that the glucosamine treatment produced noticeable improvements in symptoms. Although glucosamine administration had no antirheumatic effect evaluated by conventional measures, it seemed to have some symptomatic effects on RA.