Lovastatin is a secondary metabolite of certain filamentous fungi. It is one of thernmembers of the drug family, statins. Lovastatin, inhibitor of cholesterolrnbiosynthesis, is widely prescribed for the treatment of hypercholesterolemia. Statinsrnhave also recently been shown to inhibit HIV-1 infection by targeting cholesterol inrnthe HIV and host membrane. This research was performed to determine thernproduction of lovastatin from fruit body cultivated on sugarcane bagasse and solidstaternfermentation on different substrate (Sorghum, Rice and Wheat bran) of twornPleurotus mushrooms species that are edible and commercially cultivated inrnEthiopia. The two mushrooms investigated, P. ostreatus and P. sajor-caj, grown inrnmushroom growing house on sugarcane bagasse (60% moisture content), andrnyielded an average bioconversion efficiency of 22.58% and 17.67 % respectively.rnEthyl acetate was selected as better solvent for extraction of lovastatin in lactonernform from acidified samples that were detected on Thin Layer Chromatographyrn(TLC). The crude extracts from fruit bodies of both species show positive result onrnTLC with same Retention factor (Rf= 0.57and 0.3 for lactone and acid formrnrespectively) which was identical to the standard lovastatin. The TLC result ofrnSolid-State Fermentation (SSF) on rice and wheat bran showed the presence ofrnlovastatin whereas sorghum gives a negative result. For quantification, extraction ofrnlovastatin (β-hydroxyl acid) from fruit body as well as SSF was performed withrnmixture of methanol: water (1:1 V/V) that was chosen as the most effective solventrnfor High-performance liquid chromatography (HPLC) analysis at pH 7.7. Highestrnamount of lovastatin was found from methanol: water (1:1 V/V) extracts of P.rnostreatus fruiting body (132μg/g) of dry weight followed by P. sajor-cajurn(129μg/g). Among SSF, methanol: water extracts of fermented wheat bran and ricerngave (11.7μg/g) and (3.69μg/g) of dry weight respectively. The HPLC result ofrnsamples prepared with ethyl acetate show low amount of lovastatin. The healthrnbenefits of consuming the Pleurotus mushroom particularly for individuals withrnhigh plasma cholesterol as well as HIV infection is promising and it grows on arnvariety of agricultural residues with high bioconversion efficiency.