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The efficacy of milk thistle, Silybum  marianum methanolic extract was investigated on the third instar larvae of cotton bollworm, Helicoverpa armigera (Hübner). The experiments were done at 25±1 °C, 65±5 RH and photoperiod of 16:8 (L: D) h. The LC50 and LC20 values were estimated 10449 and 5654 ppm, respectively. One hundred microliters of the plant extract at 5654 ppm was added to 0.9 grs of artificial diet. Nutritional indices, crustacean cardioactive peptide (CCAP) content and digestive enzymatic (α-amylase and protease) activities were measured after 72 h. Plant extract decreased nutritional indices including approximate digestibility (AD), relative growth rate (RGR), relative consumption rate (RCR), efficiency of conversion of ingested food (ECI) and efficiency of digested food (ECD). Methanolic extract of S. marianum decreased α-amylase and protease activities in the midgut of H. armigera. The activity of α-amylase from 194 mU in control decreased to 86.8 mU in treatment. It also decreased protease activity from 108.2 mU in control to 60.6 mU in treatment. Incubation of dissected midgut with CCAP increased α-amylase and protease activities in H. armigera whereas the buffer alone had no effect. Feeding on artificial diet containing methanolic extract of S. marianum caused CCAP level in the midgut of the insect to decrease. Feeding on artificial diet containing methanolic extract of  S. marianum inhibits release of CCAP in the midgut and leads to reduction of α-amylase and protease activities.