The leaf extracts of three endemic species of Pandanus namely, P. luzonensis, P. panayensis, and P. simplex were investigated for their safety profile and anti-inflammatory property. The Approximate Lethal Dose (ALD) was established through acute oral toxicity test. Carrageenan-induced rat paw edema assay assessed the anti-inflammatory property. Each treatment group received assigned dose of extract (250, 500, 1000 mg/kg BW), 1% Tween 80 and diclofenac sodium (100 mg/kg BW) for the negative and positive control groups, respectively. The ethanol leaf extract P. panayensis at 500 mg/kg BW showed sustained inflammatory inhibition for 6 hours of observation with comparable inhibitory activity with diclofenac sodium (ave p=0.970). Histopathology of the inflamed paw tissues showed mild inflammation. IC 50 against COX-1 and 2 are 610.69 ug/mL and >1000 ug/mL respectively against <10 ug/mL of Indomethacin as standard. These results suggest that all Pandanus leaf extracts have an ALD greater than 2000 mg/kg BW while P. payanensis extracts may serve as potential sources of anti-inflammatory agents. This activity may be contributed by flavonoids, steroids, terpenoids and fatty acid which were identified by Liquid Chromatography-Mass Spectrometry.