The present invention provides cell permeable NF-.kappa.B inhibitors consist of a polypeptide derived from the p65 subunit of NF-.kappa.B and a protein transduction domain derived from antennapedia third helix sequence. The inhibitor suppressed NF-.kappa.B activation induced by TNF, LPS, IL-1, okadaic acid, PMA, H.sub.2O.sub.2 and cigarette smoke condensate. NF-.kappa.B-regulated reporter gene expression induced by TNF, TNFR1, TRADD, TRAF2, NIK, IKK and p65 was suppressed by the inhibitor. The inhibitor enhanced TNF- and chemotherapeutic agent-induced apoptosis. Overall these results demonstrate a NF-.kappa.B inhibitor that can selectively inhibit NF-.kappa.B activation induced by various inflammatory stimuli, downregulate NF-.kappa.B mediated gene expression and upregulate apoptosis.