UAVNs (unmanned aerial vehicle networks) may become vulnerable to threats and attacks due to their characteristic features such as highly dynamic network topology, open-air wireless environments, and high mobility. Since previous work has focused on classical and metaheuristicbased approaches, none of these approaches have a self-adaptive approach. In this paper, the challenges and weaknesses of previous methods are examined in the form of a table. Furthermore, we propose an agent-based self-protective method (ASP-UAVN) for UAVNs that is based on the Human Immune System (HIS). In ASP-UAS, the safest route from the source UAV to the destination UAV is chosen according to a self-protective system. In this method, a multi-agent system using an Artificial Immune System (AIS) is employed to detect the attacking UAV and choose the safest route. In the proposed ASP-UAVN, the route request packet (RREQ) is initially transmitted from the source UAV to the destination UAV to detect the existing routes. Then, once the route reply packet (RREP) is received, a self-protective method using agents and the knowledge base is employed to choose the safest route and detect the attacking UAVs. The proposed ASP-UAVN has been validated and evaluated in two ways: simulation and theoretical analysis. The results of simulation evaluation and theory analysis showed that the ASP-UAS increases the Packet Delivery Rate (PDR) by more than 17.4, 20.8, and 25.91%, and detection rate by more than 17.2, 23.1, and 29.3%, and decreases the Packet Loss Rate (PLR) by more than 14.4, 16.8, and 20.21%, the false-positive and false-negative rate by more than 16.5, 25.3, and 31.21% those of SUAS-HIS, SFA and BRUIDS methods, respectively.An unmanned aerial vehicle (UAV) is, in fact, an aircraft flying with no human pilot on board. Instead, an operator or the on-board computer systems control autonomously its flight either remotely. By developments in computing, device miniaturization and communication, other flying objects including quadcopters, gliders, and balloons could be also included in UAVs. Historically, military operations utilized in missions imposing high-risk levels to human pilots. However, more applications were recently found in civilian domains for UAVs. They involve rescue and search operations, inspection, and policing [1,2, and 3]. Figure 1 and 2 shows two examples of Civil applications. The setup involves multiple components and numerous links to communication. The task of each link is to transmit certain kinds of information and data. Generally, based on the kind of transmitted information, 3 various types of links should exist in these networks, i.e. radio communication, Satellite link, and U2U. The radio communication links transmit telemetry data, control audio, and video information. Furthermore, the task of satellite links is to carry GPS, meteorological, and weather information, along with the data transferred by the radio communication links. UAV applications in the field of Civil have been added to the paper in detail as the f...