A series of 1-phenyl-3-(4-phenylthiazo-2-yl) urea derivatives 3a-f, 4a-f, and 5a-f have been synthesized to meet the structural requirements essential for anti-inflammatory and antimicrobial properties. Target compounds were synthesized according to a new and convenient strategy. The strategy involves the reaction of 2-amino-4-phenylthiazoles 1a-c with ethyl chloroformate to afford ethyl 4-(substituted)phenylthiazol-2-ylcarbamates 2a-c followed by reaction with the appropriate amines either in a highly boiling point aprotic solvent or solvent free condition. Most of the target compounds showed potent antibacterial activity that equipotent or higher than ampicillin. Also, they were evaluated for their in vivo anti-inflammatory activities in rats compared to indomethacin. Four compounds 3b, 3e, 4e and 5e proved to be the most active anti-inflammatory agents in the present study with superior GI safety profile and good safety margin compared to indomethacin. In abases of molecular modeling; all synthesized 1,3-disubstituted ureas were subjected to docking simulation into active sites of human soluble epoxide hydrolase (sEH).