15-Deoxy-delta12, 14-prostaglandin J(2) (15d-PGJ(2)) is an endogenous anti-inflammatory lipid derived from PGD(2). One potential mechanism for its activity is the covalent modification of cellular proteins, via a reactive α,β-unsaturated carbonyl group in its cyclopentenone ring, which in turn alters protein function. In order to identify the candidate target proteins covalently modified by 15d-PGJ(2) in human aortic endothelial cell (EC), EC was treated with biotinylated-15d-PGJ(2), the modified proteins extracted by Neutravidin affinity-purification and the proteins identified by LTQ Orbitrap mass spectrometer. Classification of the 358 identified proteins was performed using PANTHER classification system (www.pantherdb.org), showing that the proteins mapped to metabolic process, cellular process, and transport activity. This protein data set highlights the potential for 15d-PGJ(2) to covalently modify cellular proteins and provides a source of data that will aid further studies on the mechanism of action of this endogenous regulator of inflammation.