In previous studies, the thiourea derivatives of non-steroidal anti-inflammatory drugs demonstrated significant anti-inflammatory activity. In this pilot study, three thiourea derivatives of naproxen were selected from the initial group of synthesized compounds for evaluation of anti-inflammatory activity using carrageenan induced paw edema model of acute inflammation. Analyzed compounds contained ethyl ester of L-phenylalanine, p-methoxyaniline and p-ethoxyaniline in the side chains. Wistar albino male rats were divided into 9 test groups and 4 control groups. Test groups were treated with different oral doses of selected thiourea derivative of naproxen: 2.5 mg/kg, 5 mg/kg and 10 mg/kg body weight. Three control groups were treated with 2.5 mg/kg, 5 mg/kg and 10 mg/kg body weight of naproxen and one control group was treated with solvent 1% DMSO. The thickness of the left paw tissue of each rat was measured using a Digital Vernier caliper at the following time intervals: immediately before inducing inflammation and 1, 2, 3 and 4 hours after inflammation. All tested compounds in every tested dose in the fourth hour after carrageenan administration showed a statistically significant (p < 0.05) inhibitory effect on the increase of rat paw edema compared to control, except for L-phenylalanine ethyl ester derivative in dose of 5 mg/kg and p-ethoxyaniline derivative in dose of 2.5 mg/kg. The highest percentage of inhibition was exhibited by L-phenylalanine ethyl ester and p-methoxyaniline derivatives (10 mg/kg) in the last hour (81.81%). According to obtained results, L-phenylalanine ethyl ester derivative stood out for its dose- and time-dependent anti-inflammatory effect.