Abstract: A study on the effect of a local medicinal mushroom, Laetiporus sp. (Polyporaceae) extract on total blood cholesterol level has been conducted using Wistar rats with high cholesterol feed and prophylthiouracil (PTU) as hypercholesterolemia inducing agent. The study was aimed to evaluate the inhibition and reduction effect of the dried (hot water) extract of grain grown mycelia on hypercholesterolemia of the rat model. The rats were randomly classified into tested group and control group, each group consists of six rats. After a preliminary study, two doses level of the extract, i.e., 55 and 110 mg kg-1 b.wt. were tested, respectively. Commercial lovastatin tablet at a dose of 1.8 mg kg-1 b.wt. was also incorporated in the test as reference medicine. Total blood cholesterol level was observed once a week over 4 weeks. The trial was also conducted on human by involving 19 volunteers. They were asked to consume one Laetiporus sp. capsule per day after meal before going to bed over 30 days. The fungal extract at dose 55 mg kg-1 b.wt. could inhibit the blood cholesterol level by an average of 11.0% and dose 110 mg kg-1 b.wt. could inhibit by an average of 19.0% compared to commercial lovastatin at dose 1.8 mg kg-1 b.wt. which could inhibit at an average of 14.6% over 4 weeks. On the other hand, dose 110 mg kg-1 b.wt. could reduce blood cholesterol level by an average of 11.4%, compared to commercial lovastatin tablet which could reduce by an average of 5.5% over 4 weeks. In addition, blood cholesterol level was found to be reduced in 14 out of 19 (73.6%) of human volunteers while 5 out of 19 (26.4%) were increased. It is concluded that the mycelial extract of Laetiporus sp. is potential to be used as an anti hypercholesterolemia agent.