Apoptosis, differentiation, and proliferation are cellular responses which play a pivotal role in wound healing. During this process PPARβ translates inflammatory signals into prompt keratinocyte responses. We show herein that PPARβ modulates Akt1 activation via transcriptional upregulation of ILK and PDK1, revealing a mechanism for the control of Akt1 signaling. The resulting higher Akt1 activity leads to increased keratinocyte survival following growth factor deprivation or anoikis. PPARβ also potentiates NF-κB activity and MMP-9 production, which can regulate keratinocyte migration. Together, these results provide a molecular mechanism by which PPARβ protects keratinocytes against apoptosis and may contribute to the process of skin wound closure.