Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and lethal interstitial lung disease characterized by consistent pulmonary inflammation. Although protein kinase C delta (PKC delta) is involved in broad scope cellular response, the role of PKC delta in IPF is complicated and has not been fully defined yet. Here, we reported that PKC delta deficiency (PKC delta(-/-)) aggravated bleomycin (BLM)-induced pulmonary fibrosis and inflammation. Upon challenge with BLM, the pulmonary capillary permeability, immune cell infiltration, inflammatory cytokine production, and collagen deposition were enhanced in PKC delta(-/-) mice compared to that in PKC delta(+/+) mice. In response to poly(I:C) stimulation, PKC delta deficient macrophages displayed an increased production of IL-1 beta, IL-6, TNF-alpha, and IL-33, which were associated with an enhanced NF-kappa B activation. Furthermore, we found that PKC delta could directly bind to and phosphorylate A20, an inhibitory protein of NF-kappa B signal. These results suggested that PKC delta may inhibit the NF-kappa B signaling pathway via enhancing the stability and activity of A20, which in turn attenuates pulmonary fibrosis, suggesting that PKC delta is a promising target for treating pulmonary fibrosis.