Abstract: Obesity has been a world-wide health problem and associated with many degenerative diseases. Two approved anti-obesity compounds, sibutramine and orlistat, have various serious side effects which limit their uses. IgY anti lipase will inhibit the activity of pancreatic lipase in the gastrointestinal tract. The objective of this study was to evaluate the effectivity of IgY anti lipase obtained from yolk as pancreatic lipase inhibitor for prevention of obesity. IgY anti lipase was obtained from the yolk of hens immunized with porcine pancreatic lipase and was purified with sodium sulphate precipitation. The protein was analyzed by SDS-PAGE and was identified by Immunoblotting. The ability of IgY anti lipase to inhibit pancreatic lipase was tested by ELISA colorimetric microplate assay at five grades of concentration. Yolk containing IgY anti lipase was then tested in rabbit to evaluate its ability to inhibit fat absorption in vivo. The result showed that IgY contained two proteins with molecular weights of 61.2 and 26.9 kDa and was positively reacted with the rabbit anti chicken coupled with HRP. IgY anti lipase and orlistat did not differ in inhibition capacity at various concentrations (p>0.05). The inhibition capacity of IgY obtained from unimmunized hen was significantly lower than IgY anti lipase and orlistat (p<0.05). Yolk containing IgY anti lipase also had the ability to inhibit dietary fat absorption in vivo, but its inhibition capacity was lower than orlistat (p<0.05). It is concluded that IgY anti lipase could be used to inhibit fat absorption to prevent obesity.