Objective: The present study was carried out to evaluate SSF process for the production of avermectin by Streptomyces avermitilis NRRL 8165 using easily available grains, millets and some agricultural by-product.Methods: Various substrates were screened for their ability to support avermectin production. Different parameters to maximize the yield of avermectin by S. avermitilis NRRL 8165 under SSF were optimized by conventional one factor at a time approach and parameters optimized earlier were adopted for the subsequent study.Results: Sorghum seeds used as solid substrate supported maximum growth and total avermectin production (4.6 mg g-1 dry substrate). The optimum values for maximum avermectin production were: moistening medium containing g l-1 KH2PO4 1; MgSO4.7H2O 0.4, inoculum size 20 % (24 h old culture in yeast extract-malt extract dextrose medium) v/w of initial dry substrate, substrate particle size 0.5 to 4 mm, incubation temperature 28 °C, initial moisture level 105%, incubation period of 15 d, 8 % w/w sucrose and 5% w/w soyameal. The avermectin yield with optimized fermentation condition was 5.8 mg g-1 dry substrate which is 1.3 fold higher as compared to non-optimized condition.Conclusion: Avermectin produced by S. avermitilis are widely used as an anthelmintic agent in the medical, veterinary and agricultural applications. In comparison with submerged fermentation, SSF can become an alternative cost-effective method for the production of avermectin. This report demonstrates the feasibility of employing agro-based substrate, that could reduce antibiotics production cost
