The purpose of this experiment was to study the effects of different cultural patterns on the growth performance, serum activity indicator, and immune responses of Litopenaeus vannamei. Two pilot-scale culture models of Litopenaeus vannamei, recirculating aquaculture system (RAS) and biofloc technology system (BS), were constructed in a greenhouse, each of which was 3 parallel. 100 000 larvae of Litopenaeus vannamei were placed in parallel, and the initial culture density was 500 per m3. The water quality indicator of culture water was measured every other day, and after 100 days of feeding, the growth indicator, serum antioxidant activity indicator, and immune responses of Litopenaeus vannamei were measured. The results showed that there was no significant difference in ammonia nitrogen, nitrite, nitrate, temperature, pH value, and dissolved oxygen between RAS and BS groups, but nitrite accumulation in the BS group was nearly 20 days, which affected the growth of Litopenaeus vannamei. The specific growth rate, survival rate, and final density of the BS group were significantly lower than those of the RAS group (p<0.05), but there was no significant difference in feed conversion factor (FCR) and condition factor (CF). There was no significant difference in the intestinal flora of shrimp in the two culture modes at the phylum level and significant difference at the genus level (P<0.05), with the highest abundance of norank_f__JG30-KF-CM45 in the RAS culture mode and the highest abundance of the genus Amaricoccus in the BS culture mode. In conclusion, RAS cultivation can achieve stable and controllable water quality indexes and then improve the growth performance of shrimp, but the production cost is slightly higher than BS cultivation.