This study was aimed to develop the Thai silkworm model for screening glucose lowering effect. Thai silkworms were fed with 10% glucose or 10% sucrose diet to induce hyperglycemia. Human insulin and some oral hypoglycemic agents used in the clinical setting such as glibenclamide, metformin and acarbose were utilized to lower the glucose level in silkworm hemolymph. Later this hyperglycemic silkworm model was tested with ECa 233. The results showed that 10% glucose or 10% sucrose diet fed for 1 hr can increase sugar level in Thai silkworm hemolymph and sugar level reach the maximum concentrations of 7.37 ± 0.07 and 7.70 ± 0.08 mg/ml at 5 and 4 hr after the diet were taken out, respectively. For toxicity testing, LD50 of glibenclamide, metformin, acarbose and ECa 233 in Thai silkworm were 0.047, 0.041, > 25 and 1.46 mg/g respectively. Human insulin, glibenclamide and acarbose exhibited the hypoglycemic effect in Thai silkworm model with statistical significance comparing with 0.9% NaCl injected group (P< 0.01) and in concentration dependent manner, whereas metformin could not lower sugar level. Using this model to test ECa 233, the results showed that ECa 233 also exhibited hypoglycemic effect as shown by a statistical significance (P< 0.01) decrease of sugar level in Thai silkworm hemolymph in a concentration dependent manner as compared to the 0.9% NaCl injected group. These results suggested that Thai silkworm model can be proposed as an alternative for screening of glucose lowering effect in Thai herbal extract, chemical substances having mechanism of action similar to oral hypoglycemic drugs or insulin used in this study. Furthermore, the use of this hyperglycemic silkworm model can also save time and cost in some extent for drug research and development.