The present invention provides a method of reducing microloading effect by using a photoresist layer as a buffer. The method includes: providing a substrate defined with a dense region and an isolated region. Then, a dense feature pattern and an isolated feature pattern are formed on the dense region and the isolated region respectively. After that, a photoresist layer is formed to cover the isolated region. Finally, the substrate and the photoresist layer are etched by taking the dense feature pattern and the isolated feature pattern as a mask.