The aim of the present study was to investigate the effect of meloxicam and meloxicam with misoprostol on prostaglandin E2 (PGE2) and prostaglandin I2 (PGI2) serum concentration, as well as on gastrointestinal permeability. NSAIDs, such as meloxicam, have gastrointestinal side effects, which are due to prostaglandins depletion and topical damage. Seven adult beagle dogs were included in the study. Three different 20 days long treatments were carried out (placebo, meloxicam and meloxicam with misoprostol). The same seven dogs participated in all three treatments. On days 1 to 10 the dogs received placebo, meloxicam or meloxicam together with misoprostol PO. Dogs were than monitored from day 11 to 20. Samples for serum PGE2 and PGI2 concentration and plasma lactulose, mannitol and sucrose concentration determination were drawn on day 0, 2, 6, 11 and 20. Lactulose/mannitol (L/M) index was calculated. Treatment with meloxicam and meloxicam with misoprostol resulted in lower PGE2 and PGI2 serum concentrations in comparison to the placebo. L/M index and sucrose plasma concentration were increased in both groups in comparison to the placebo. According to the results of the study, meloxicam has altered gastrointestinal permeability and depleted prostaglandins production. Misoprostol was shown to be an effective preventing treatment