In the present study, the effect of intrauterine infusion of Zataria multiflora extract on the clinical endometritis was investigated. Vaginal examination, transrectal palpation and ultrasonography were used to inspect the genital tract at 30-40 days in milk and two weeks later the same approach was applied. Cows with clinical endometritis were randomly divided into three treatment groups: Z. multiflora extract (n = 56), penicillin + streptomycin (pen + strep, n = 55), and placebo (n = 20). Cervical cytology, reagent strip test and cell counting by means of Neubauer hemocytometer were carried out in both examinations. Clinical cure rate of cows with endometritis of score 1 were 45.5, 34.5 and 53.6% in placebo, pen + strep and Z. multiflora, respectively. Clinical cure rate of cows with endometritis of score 2, 3 were 66.7, 84.6 and 56.0% in placebo, pen + strep and Z. multiflora, respectively. Overall, proportions of successfully treated cows were 55.0, 58.2 and 54.7% in placebo, pen + strep and Z. multiflora, respectively (p > 0.05). In placebo, none of the parameters were significantly different between first and second examination, while we found the significant differences in percentage of neutrophils and leukocyte esterase activity in other groups (p < 0.05). First service conception rate of cows was higher in Z. multiflora compared to other groups; however, this difference was not significant. In conclusion, pen + strep and Z. multiflora extract can be effective on the clinical endometritis and may improve reproductive performance. The extract of Z. multiflora can be useful as an alternative therapy for treatment of clinical endometritis in lactating dairy cows. (C) 2016 Urmia University. All rights reserved.