p38α mitogen activated protein kinase(MAPK) inhibitors provide a novel approach for the treatment of inflammatory disorders.A series of fifteen pyrazolyl urea derivatives(3a-o) were synthesized and evaluated for their p38α MAPK inhibition and antioxidant potential.Compounds 3a-e,3g and 3h showed low micromolar range potency(IC_(50) values ranging from 0.037 ±1.56 to 0.069± 0.07μmol/L)compared to the standard inhibitor SB 203580(IC_(50) = 0.043 + 3.62μmol/L) when evaluated for p38αMAPK inhibition by an immunosorbent-based assay.Antioxidant activity was measured by a 2,2’-diphenyl-1-picryl hydrazyl radical(DPPH) free radical scavenging method and one of the compounds,3c,showed better percentage antioxidant activity(75.06%) compared to butylated hydroxy anisole(71.53%)at 1 mmol/L concentration.Compounds 3a-e,3g and 3h showed promising in vivo anti-inflammatory activity(ranging from 62.25%to 80.93%) in comparison to diclofenac sodium(81.62%).The ulcerogenic liability and lipid peroxidation activity of these compounds were observed to be less in comparison to diclofenac sodium.These compounds also potently inhibited the lipopolysaccharide(LPS)-induced TNF-αrelease in mice(ID_(50) of 3a-c = 19.98,11.32 and 9.67 mg/kg,respectively).Among the screened compounds,derivative 3c was found to be the most potent and its binding mode within the p38α MAPK is also reported. A series of fifteen pyrazolyl urea derivatives (3a-o) was synthesized and evaluated for their p38 [alpha] MAPK inhibition and antioxidant potential. Compounds 3-A, 3g and 3h showed low micromolar range potency (IC 50 values ​​ranging from 0.037 ± 1.56 to 0.069 ± 0.07 μmol / L) compared to the standard inhibitor SB 203580 (IC 50 = 0.043 + 3.62 μmol / L) when evaluated for p38αMAPK inhibition by an immunosorbent-based assay. Antioxidant activity was measured by a 2,2’-diphenyl-1-picrylhydrazyl radical (DPPH) free radical scavenging method and one of the compounds, 3c, showed better percentage antioxidant activity (75.06% (71.53%) at 1 mmol / L concentration .Compounds 3a-e, 3g and 3h showed promising in vivo anti-inflammatory activity (ranging from 62.25% to 80.93%) in comparison to diclofenac sodium (81.62% The ulcerogenic liability and lipid perox idation activity of these compounds were observed to be less in comparison to diclofenac sodium.These compounds also potently inhibited the lipopolysaccharide (LPS) -induced TNF-α release in mice (ID_ (50) of 3a-c = 19.98, 11.32 and 9.67 mg / kg, respectively). Among the screened compounds, derivative 3c was found to be the most potent and its binding mode within the p38α MAPK is also reported.