The purpose of this study was to assess the effects of systemic zinc sulfate in the treatment of recurrent aphthous stomatitis (RAS) by atomic absorption spectrophotometry. The study was carried out on 40 patients with RAS. The first group consisted of 20 subjects with RAS who were administered zinc sulfate (220 mg) once per day for one month. In the second group, there were 20 subjects with RAS who were administered placebo (saccharose). Results showed that the levels of serum zinc before treatment were under the normal value in the 42.5% percent of the patients with RAS. Saliva ALP, serum zinc, serum albumin, and serum alkaline phosphates activity for group II were significantly lower than those for group I after treatment (p < 0.01). After 1 month of zinc therapy the aphthae reduced and did not reappear for 3 months. The empirical use of systemic zinc sulfate supplementation in the treatment of RAS is recommend.