A 32 central composite experimental design was performed with the aim of optimizing xylanase production by Chaetomium thermophilum IMI 291753 grown on wheat straw in submerged cultures. Various carbon and nitrogen sources were consecutively optimized, and wheat straw and sodium nitrate were the selected substrates to test the effect of two variables on xylanase production. A second-order quadratic model and a response surface method showed that the optimum conditions for xylanase production were 3.9% (w/v) wheat straw and 0.7% (w/v) sodium nitrate.