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Utilizing collagen of sheep bone as material to get immunocompetent peptide, enzymatic hydrolysis conditions were optimized using quadratic regression general rotation design. The effect of temperature (T), time (t), enzyme/substrate (E/S) ratio, and substrate concentration (S) on the amount of tricarboxylix acid cycle (TCA) soluble peptides were investigated. The content of soluble peptide in the acquisition was measured by Folin-hydrozybebzebe method, and the correlation between soluble peptide content and immunocompetence was analyzed by SAS software. The best enzymatic hydrolysis condition was gotten from Design Expert 7.1.2 software. The optimal condition under which immunocompetent peptides could be prepared was 1 576 U g-1 (E/S), 64.05℃ (T), 0.271 kg L-1(S), and 7.22 h (t). The correlation coefficient between TCA soluble peptides and the immuneocompetence was 0.045 < r0.05= 0.355, which indicated that they had no significant correlation. The result showed that the soluble peptide contained immunocompetent peptides which content was independent of immunocompetence in the hydrolasates.