Avermectins, are pesticides of fermentation products with high efficacy and low toxicity and play important roles in food and agricultural product safety, animal and human health. Ivermectins, the derivatives of avermectins, are used to treat Onchocerciasis, also known as River Blindness. Thanks to these discoveries, more than 200 million Africans are lucky to be exempted from blindness. Great efforts have been made on better understanding of the microbial production system of avermectins through genetic engineering in China. Starting from scratch, Chinese avermectin industry has experienced a comprehensive technological innovation with significantly improved yield, titer and productivity of avermectins, and became the exclusive supplier for the global market. The success of avermectin industry innovation in China not only shed lights on the intelligent yield improvement of other microbial natural product drugs, but also gained wide international recognition. We provide here an overview of the discovery and development of basic and applied research of avermectins, especially historical evolution of avermectins made in China, which will benefit industrial development of microbial drugs in China.