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The problem might be caused by ScanMail transport agent issues.

To resolve the issue:

 
If you are using Microsoft Exchange 2013 SP1, make sure you have installed SMEX version 11.0 Patch 1 or SMEX 12.0, before performing the procedure below to prevent issues. For more information, refer to the article, Compatibility issue between Microsoft Exchange 2013 SP1 and ScanMail for Exchange (SMEX) 11, 12 or Messaging Security Agent (MSA).
  1. Run the Microsoft Fix It tool by following this article: Third-party transport agents cannot be loaded correctly in Exchange Server 2013
  2. Install the ScanMail SMTP Receive Agent and Routing Agent via Microsoft PowerShell.
     
    Make sure to change the path "C:\Program Files\Trend Micro\Smex\hookE12TransportAgent.dll" to the correct path where SMEX is installed.
    • For ScanMail SMTP Receive Agent:

      Install-TransportAgent -Name "ScanMail SMTP Receive Agent" -TransportAgentFactory "TrendMicro.SMEX.hookE12TransportAgent.hookE12SmtpReceiveAgentFactory" -AssemblyPath "C:\Program Files\Trend Micro\Smex\hookE12TransportAgent.dll"; Set-TransportAgent -Identity "ScanMail SMTP Receive Agent" -Priority 1; Enable-TransportAgent -Identity "ScanMail SMTP Receive Agent"

    • For ScanMail Routing Agent:

      Install-TransportAgent -Name "ScanMail Routing Agent" -TransportAgentFactory "TrendMicro.SMEX.hookE12TransportAgent.hookE12RoutingAgentFactory" -AssemblyPath "C:\Program Files\Trend Micro\Smex\hookE12TransportAgent.dll"; Set-TransportAgent -Identity "ScanMail Routing Agent" -Priority 2; Enable-TransportAgent -Identity "ScanMail Routing Agent"

  3. Restart the MSExchangeTransport Service in services.msc.
  4. Verify if the ScanMail transport agents were successfully installed by running the “Get-TransportAgent” command.
    You should be able to see the following on the list:
    ScanMail Routing Agent
    ScanMail SMTP Receive Agent

If the procedure does not resolve the issue, download the current version of SMEX from the Download Center and install it.

If the issue persists, generate the log files using the latest version of Case Diagnostic Tool (CDT) and contact Trend Micro Technical Support.