Paclitaxel is the most profitable anticancer drug in history; however, the yield of paclitaxel from fungal fermentation is still far from the commercial purpose. In this study, two local fungal endophytes of Aspergillus fumigants TXD105 and Alternaria tenuissima TER995 were used as promising sources for the production of paclitaxel under submerged fermentation. In order to improve the paclitaxel magnitude, response surface methodology optimization program was applied to medium constituents that showed the high contribution to paclitaxel production. Moreover, improvement of paclitaxel production by UV and gamma irradiation was studied. The use of response surface methodology resulted in significant increases in the paclitaxel production of the two strains by 16.25 and 19.86%, respectively. Furthermore, the production of paclitaxel by the two strains was greatly enhanced by the application of UV and gamma irradiation. Using 0.75 KGy of gamma irradiation, paclitaxel concentrations were intensified to 495.31 and 195.41 mu g L-1, respectively. The obtained paclitaxel concentrations by the two strains irradiated by UV for 30 min were 1.16 and 1.20 fold, respectively of their controls. These findings showed a great potential for production of paclitaxel by fungal cultures in industrial scale that indicate the future possibility to reduce the cost of producing fermentation-based drugs.