The present study describes degradation behavior of cefixime trihydrate (CEF-3H2O) which was investigated under different stress conditions of sun light, UV light at 254 nm and some pharmaceutical excipients using HPLC. Stability - indicating methods RP-HPLC were modified that could separate the drug from its degradation products formed under these stress conditions. Degradation was found to occur under sun light and UV light, two major decomposed products were successfully resolved on a C18 column (waters spherisorb 25 cm × 4.6 mm,5μm),utilizing mobile phase of tetra butyl ammonium hydroxide solution (0.03M aqueous) pH adjusted to 6.5 with diluted orthophospharic acid (10 % aqueous) and acetonitrile in a ratio of 3:1 respectively. Mobile phase was delivered at the flow rate of 1.0 ml/min. Ultra violet detection was carried out at 254 nm. Separation was completed within 4.62, 11.05 minutes respectively. The method was validated with respect to linearity, precision, accuracy, selectivity, specificity and ruggedness. The method was specific to drug and also selective to degradation products.TLC technique was used to separate two decomposed products which were appeared at (Rf) 0.65, 0.78 respectively for UV decomposed and 0.39, 0.65 respectively for sun decomposed. Some pharmaceutical excipinents were found to decrease the reaction rate of sun, UV, and thermal decomposition of cefixime trihydrate in aqueous media. Other pharmaceutical excipinents were found to increase the reaction rate of cefixime trihydrate sun, UV, and thermal decomposition.