Kendala yang sering dialami pembudidaya ikan lele salah satunya yaitu serangan motile Aeromonas septicemia (MAS). Vaksinasi melalui perendaman merupakan cara yang efektif untuk meningkatkan sistem imun pada tubuh ikan lele, namun kurang memberikan hasil yang optimal sehingga perlu adanya penambahan metode infiltrasi hiperosmotik untuk memaksimalkan penyerapan vaksin. Penelitian ini bertujuan untuk menentukan kisaran salinitas yang baik dalam memaksimalkan penyerapan vaksin Aeromonas hydrophila pada ikan lele. Penelitian ini menggunakan metode eksperimental rancangan acak lengkap dengan lima taraf perlakuan dan tiga kali ulangan, antara lain kontrol negatif (Kn), kontrol positif (Kp), perendaman salinitas 3 ppt (P1), perendaman salinitas 6 ppt (P2), dan perendaman salinitas 9 ppt (P3) pada ikan lele berukuran 12-15 cm. Parameter yang diamati antara lain titer antibodi, relative percent survival, survival rate (SR), total eritrosit, total leukosit, kualitas air, dan gejala klinis. Hasil penelitian menunjukkan nilai tertinggi yaitu pada P2 (6 ppt) dengan nilai titer antibodi sebesar 8,0 ± 0,0, relative percent survival 100%, survival rate 100%, dan total eritrosit 2,80 x 106 sel mm-3, namun total leukosit pada P2 (6 ppt) menunjukkan nilai terendah karena leukosit melawan serangan patogen sehingga jumlah sel menurun. Disimpulkan bahwa perendaman dalam salinitas 6 ppt merupakan salinitas terbaik pada ikan lele dan berbeda nyata (P<0,05) dengan perlakuan lainnya karena proses penyerapan vaksin terjadi secara maksimal sehingga dapat meningkatkan sistem imun ikan lele.One of the obstacles often experienced by catfish farmers is attacks by the motile Aeromonas septicemia (MAS). Vaccination through immersion is an effective way to improve the immune system in the body of catfish, but it does not provide optimal results so it is necessary to add a hyperosmotic infiltration method to maximize vaccine absorption. This study aimed to determine an optimum salinity range to maximize the absorption of the Aeromonas hydrophila vaccine in catfish. This study used a completely randomized design experimental method with five treatment levels and three replications, including negative control (Kn), positive control (Kp), 3 ppt salinity immersion (P1), 6 ppt salinity immersion (P2), and 9 ppt salinity immersion (P3) in catfish sizing 12-15 cm. The parameters observed included antibody titer, relative percent survival, survival rate (SR), total erythrocytes, total leukocytes, water quality, and clinical symptoms. The results of the study showed that the highest value was at P2 (6 ppt) with an antibody titer value of 8.0 ± 0.0, relative percent survival 100%, survival rate 100%, and total erythrocytes 2.80 x 106 cells mm-3, while total leukocytes in P2 (6 ppt) showed the lowest value because leukocytes fought against pathogen attacks so that the number of cells decreased. It was concluded that immersion in 6 ppt salinity was the best salinity for catfish and was significantly different (P<0.05) from other treatments because the vaccine absorption process occurred optimally so that it could improve the catfish's immune system.