Several million people across the globe are at risk for upper aerodigestive cancer. Promoting the activation of PPARγ in precancerous lesions is a novel strategy of nuclear receptor activation that shows promising chemopreventive potential. Natural products which upregulate PPARγ may therefore be an inexpensive, low toxicity approach to the prevention of upper aerodigestive cancer. This study examined several natural products which either had demonstrated chemopreventive ability or were being used in ongoing chemopreventive studies at the University of Minnesota Masonic Cancer Canter. These products, which included inositol hexaphosphate, eucalyptol, nicotinamide, nicotinic acid, trans-chalcone, 4'-methoxychalcone, and resveratrol, were tested for their ability to upregulate PPARγ DNA binding activity. Resveratrol, a product naturally found in red wine, demonstrated positive results in screening studies of PPARγ activation in aerodigestive cancer cell lines. These data show that resveratrol is an important chemopreventive target due to its ability to upregulate PPARγ. Further investigation could examine the downstream differentiation effects of resveratrol via PPARγ pathways.