The p38 protein kinase is a serine-threonine mitogen activated protein kinase, which plays an important role in inflammation and arthritis. p38 subgroup of the mitogen activated protein kinasesuper family has four isoforms: p38α, p38β, p38δ, p38γ. p38α is involved in inflammation,proliferation, differentiation and apoptosis. The biological functions of p38β, p38δ, p38γ are notunderstood completely. Many p38α inhibitors with diverse chemical structures and modes of protein interaction have been designed on the basis of their ability to compete with ATPsite or Allostericsitefor binding to p38α. In the late 1970’s and early 1980’s the initial p38 chemo type, triaryl imidazole was discovered. During the last ten years a number of novel p38 chemotypes were discovered viahigh through put screening. Among several novel p38 chemotypes developed, pyrazolyl ureas and its derivatives were identified as potent and selective p38 kinase inhibitors.